Human Gene HDAC6 (uc004dks.1) Description and Page Index
  Description: Homo sapiens histone deacetylase 6 (HDAC6), mRNA.
RefSeq Summary (NM_006044): Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains which appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660805.144770.1, SRR1660803.117327.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000334136.11/ ENSP00000334061.5 RefSeq Select criteria :: based on manual assertion, conservation, expression ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chrX:48,660,487-48,683,380 Size: 22,894 Total Exon Count: 29 Strand: +
Coding Region
   Position: hg19 chrX:48,661,100-48,683,022 Size: 21,923 Coding Exon Count: 28 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:48,660,487-48,683,380)mRNA (may differ from genome)Protein (1215 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: HDAC6_HUMAN
DESCRIPTION: RecName: Full=Histone deacetylase 6; Short=HD6; EC=3.5.1.98;
FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin.
FUNCTION: In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy.
CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
COFACTOR: Binds 3 zinc ions per subunit.
SUBUNIT: Interacts with CBFA2T3, HDAC11 and SIRT2. Interacts with F-actin. Interacts with BBIP10. Under proteasome impairment conditions, interacts with UBD via its histone deacetylase 1 and UBP-type zinc-finger regions. Interacts with CYLD. Interacts with ZMYND15 (By similarity). Interacts with DDIT3/CHOP.
INTERACTION: Q9HCU9:BRMS1; NbExp=2; IntAct=EBI-301697, EBI-714781; Q62623:Cdc20 (xeno); NbExp=2; IntAct=EBI-301697, EBI-2256532; P00533:EGFR; NbExp=8; IntAct=EBI-301697, EBI-297353; P03409:tax (xeno); NbExp=4; IntAct=EBI-301697, EBI-5236464;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=It is mainly cytoplasmic, where it is associated with microtubules.
PTM: Phosphorylated by AURKA.
PTM: Ubiquitinated. Its polyubiquitination however does not lead to its degradation.
PTM: Sumoylated in vitro.
SIMILARITY: Belongs to the histone deacetylase family. HD type 2 subfamily.
SIMILARITY: Contains 1 UBP-type zinc finger.
SEQUENCE CAUTION: Sequence=BAA74924.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HDAC6
CDC HuGE Published Literature: HDAC6

-  MalaCards Disease Associations
  MalaCards Gene Search: HDAC6
Diseases sorted by gene-association score: chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia* (1320)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 49.39 RPKM in Pituitary
Total median expression: 932.75 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -37.6693-0.405 Picture PostScript Text
3' UTR -115.00358-0.321 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000286 - His_deacetylse
IPR023801 - His_deacetylse_dom
IPR013083 - Znf_RING/FYVE/PHD
IPR001607 - Znf_UBP

Pfam Domains:
PF00850 - Histone deacetylase domain
PF02148 - Zn-finger in ubiquitin-hydrolases and other protein

SCOP Domains:
52768 - Arginase/deacetylase

Protein Data Bank (PDB) 3-D Structure
MuPIT help

3C5K
- X-ray MuPIT

3GV4
- X-ray MuPIT

3PHD
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9UBN7
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001047 core promoter binding
GO:0003779 actin binding
GO:0004407 histone deacetylase activity
GO:0005515 protein binding
GO:0008013 beta-catenin binding
GO:0008017 microtubule binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0019899 enzyme binding
GO:0031593 polyubiquitin binding
GO:0031625 ubiquitin protein ligase binding
GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific)
GO:0042826 histone deacetylase binding
GO:0042903 tubulin deacetylase activity
GO:0043014 alpha-tubulin binding
GO:0043130 ubiquitin binding
GO:0046872 metal ion binding
GO:0048156 tau protein binding
GO:0048487 beta-tubulin binding
GO:0051787 misfolded protein binding
GO:0051879 Hsp90 protein binding
GO:0070840 dynein complex binding

Biological Process:
GO:0000209 protein polyubiquitination
GO:0006325 chromatin organization
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006476 protein deacetylation
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006515 misfolded or incompletely synthesized protein catabolic process
GO:0006886 intracellular protein transport
GO:0006914 autophagy
GO:0007026 negative regulation of microtubule depolymerization
GO:0009636 response to toxic substance
GO:0009967 positive regulation of signal transduction
GO:0010033 response to organic substance
GO:0010469 regulation of receptor activity
GO:0010506 regulation of autophagy
GO:0010634 positive regulation of epithelial cell migration
GO:0010727 negative regulation of hydrogen peroxide metabolic process
GO:0010870 positive regulation of receptor biosynthetic process
GO:0016241 regulation of macroautophagy
GO:0016575 histone deacetylation
GO:0031647 regulation of protein stability
GO:0032418 lysosome localization
GO:0032461 positive regulation of protein oligomerization
GO:0032984 macromolecular complex disassembly
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0034983 peptidyl-lysine deacetylation
GO:0035967 cellular response to topologically incorrect protein
GO:0040029 regulation of gene expression, epigenetic
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
GO:0043242 negative regulation of protein complex disassembly
GO:0045598 regulation of fat cell differentiation
GO:0045861 negative regulation of proteolysis
GO:0045892 negative regulation of transcription, DNA-templated
GO:0048668 collateral sprouting
GO:0051354 negative regulation of oxidoreductase activity
GO:0051646 mitochondrion localization
GO:0051788 response to misfolded protein
GO:0060271 cilium assembly
GO:0060632 regulation of microtubule-based movement
GO:0060765 regulation of androgen receptor signaling pathway
GO:0060997 dendritic spine morphogenesis
GO:0061734 parkin-mediated mitophagy in response to mitochondrial depolarization
GO:0070201 regulation of establishment of protein localization
GO:0070301 cellular response to hydrogen peroxide
GO:0070842 aggresome assembly
GO:0070845 polyubiquitinated misfolded protein transport
GO:0070846 Hsp90 deacetylation
GO:0070848 response to growth factor
GO:0070932 histone H3 deacetylation
GO:0071218 cellular response to misfolded protein
GO:0090035 positive regulation of chaperone-mediated protein complex assembly
GO:0090042 tubulin deacetylation
GO:0098779 mitophagy in response to mitochondrial depolarization
GO:1901300 positive regulation of hydrogen peroxide-mediated programmed cell death
GO:1903146 regulation of mitophagy

Cellular Component:
GO:0000118 histone deacetylase complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005771 multivesicular body
GO:0005829 cytosol
GO:0005874 microtubule
GO:0005875 microtubule associated complex
GO:0005881 cytoplasmic microtubule
GO:0005901 caveola
GO:0016234 inclusion body
GO:0016235 aggresome
GO:0030424 axon
GO:0030425 dendrite
GO:0031252 cell leading edge
GO:0032991 macromolecular complex
GO:0042995 cell projection
GO:0043005 neuron projection
GO:0043204 perikaryon
GO:0044297 cell body
GO:0048471 perinuclear region of cytoplasm
GO:0030286 dynein complex


-  Descriptions from all associated GenBank mRNAs
  AK302926 - Homo sapiens cDNA FLJ56474 complete cds, highly similar to Histone deacetylase 6.
AL137696 - Homo sapiens mRNA; cDNA DKFZp566E044 (from clone DKFZp566E044).
BC005872 - Homo sapiens histone deacetylase 6, mRNA (cDNA clone IMAGE:3029555), complete cds.
AK024083 - Homo sapiens cDNA FLJ14021 fis, clone HEMBA1002513, highly similar to Histone deacetylase 6.
AJ011972 - Homo sapiens mRNA for histone deacetylase-like protein (JM21).
AB020708 - Homo sapiens KIAA0901 mRNA for KIAA0901 protein.
BC069243 - Homo sapiens histone deacetylase 6, mRNA (cDNA clone MGC:78509 IMAGE:6584427), complete cds.
AK295884 - Homo sapiens cDNA FLJ54798 complete cds, highly similar to Histone deacetylase 6.
BC011498 - Homo sapiens histone deacetylase 6, mRNA (cDNA clone IMAGE:4179066), complete cds.
AK095124 - Homo sapiens cDNA FLJ37805 fis, clone BRSSN2001342, highly similar to Histone deacetylase 6.
JD216210 - Sequence 197234 from Patent EP1572962.
JD208923 - Sequence 189947 from Patent EP1572962.
JD310346 - Sequence 291370 from Patent EP1572962.
KJ902051 - Synthetic construct Homo sapiens clone ccsbBroadEn_11445 HDAC6 gene, encodes complete protein.
BT006649 - Homo sapiens histone deacetylase 6 mRNA, complete cds.
AB385398 - Synthetic construct DNA, clone: pF1KA0901, Homo sapiens HDAC6 gene for histone deacetylase 6, complete cds, without stop codon, in Flexi system.
AF132609 - Homo sapiens histone deacetylase 6 mRNA, complete cds.
BC013737 - Homo sapiens histone deacetylase 6, mRNA (cDNA clone MGC:5339 IMAGE:2984860), complete cds.
AK303012 - Homo sapiens cDNA FLJ56624 complete cds, highly similar to Histone deacetylase 6.
JF432329 - Synthetic construct Homo sapiens clone IMAGE:100073516 histone deacetylase 6 (HDAC6) gene, encodes complete protein.
KJ902052 - Synthetic construct Homo sapiens clone ccsbBroadEn_11446 HDAC6 gene, encodes complete protein.
AF174499 - Homo sapiens GR AF-1 specific histone deacetylase mRNA, partial cds.
AK127118 - Homo sapiens cDNA FLJ45175 fis, clone BRAWH3046424.
AK122954 - Homo sapiens cDNA FLJ16672 fis, clone THYMU3001883, highly similar to Histone deacetylase 6.
AK309058 - Homo sapiens cDNA, FLJ99099.
AK001543 - Homo sapiens cDNA FLJ10681 fis, clone NT2RP3000031, highly similar to Histone deacetylase 6.
AK131286 - Homo sapiens cDNA FLJ16239 fis, clone HCASM2003099, highly similar to Histone deacetylase 6.
BC013219 - Homo sapiens histone deacetylase 6, mRNA (cDNA clone IMAGE:4149706).
DQ573585 - Homo sapiens piRNA piR-41697, complete sequence.
JD313488 - Sequence 294512 from Patent EP1572962.
JD240436 - Sequence 221460 from Patent EP1572962.
JD329234 - Sequence 310258 from Patent EP1572962.
JD439183 - Sequence 420207 from Patent EP1572962.
JD337895 - Sequence 318919 from Patent EP1572962.
JD224552 - Sequence 205576 from Patent EP1572962.
JD486505 - Sequence 467529 from Patent EP1572962.
JD156553 - Sequence 137577 from Patent EP1572962.
JD448634 - Sequence 429658 from Patent EP1572962.
JD431259 - Sequence 412283 from Patent EP1572962.
JD291694 - Sequence 272718 from Patent EP1572962.
JD533543 - Sequence 514567 from Patent EP1572962.
JD445892 - Sequence 426916 from Patent EP1572962.
JD077217 - Sequence 58241 from Patent EP1572962.
JD484376 - Sequence 465400 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_ranbp2Pathway - Sumoylation by RanBP2 Regulates Transcriptional Repression
h_carm-erPathway - CARM1 and Regulation of the Estrogen Receptor

Reactome (by CSHL, EBI, and GO)

Protein Q9UBN7 (Reactome details) participates in the following event(s):

R-HSA-9008389 RUNX2 binds HDAC6
R-HSA-5324632 Dissociation of cytosolic HSF1:HSP90:HDAC6:PTGES3 upon sensing protein aggregates
R-HSA-5618331 HDAC6 deacetylates microtubules
R-HSA-9008433 RUNX2 binds CDKN1A gene promoter
R-HSA-1912388 NICD1 displaces co-repressor complex from RBPJ (CSL)
R-HSA-2220982 NICD1 PEST domain mutants displace co-repressor complex from RBPJ (CSL)
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8941326 RUNX2 regulates bone development
R-HSA-3371511 HSF1 activation
R-HSA-5617833 Cilium Assembly
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3371556 Cellular response to heat stress
R-HSA-1852241 Organelle biogenesis and maintenance
R-HSA-212436 Generic Transcription Pathway
R-HSA-1980143 Signaling by NOTCH1
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2262752 Cellular responses to stress
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-157118 Signaling by NOTCH
R-HSA-2644603 Signaling by NOTCH1 in Cancer
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-74160 Gene expression (Transcription)
R-HSA-162582 Signal Transduction
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: HDAC6_HUMAN, JM21, KIAA0901, NM_006044, NP_006035, O94975, Q96CY0, Q9UBN7
UCSC ID: uc004dks.1
RefSeq Accession: NM_006044
Protein: Q9UBN7 (aka HDAC6_HUMAN or HDA6_HUMAN)
CCDS: CCDS14306.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_006044.2
exon count: 29CDS single in 3' UTR: no RNA size: 4099
ORF size: 3648CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7496.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.